Should GB virus be used as a therapeutic vaccine to slow HIV progression?

Michael Carter

Published: 12 July 2012

Acquisition of GB
virus C (GBV-C) is associated with a 78% reduction in mortality risk for people with AIDS, investigators report in the online edition of Clinical Infectious Diseases. The
beneficial effects of GBV-C infection (often incorrectly called hepatitis G
virus) were significant even after controlling for CD4 cell count, HIV viral
load and use of antiretroviral therapy, leading an expert in infectious diseases to ask whether GB virus C ought to be considered as a therapeutic vaccine.

Dr David Gretch, the
author of an editorial accompanying the study, believes the results settle any
doubts about the protective effects of GBV-C virus infection in HIV disease. He comments: “GBV-C viremia is associated with protective effects
in persons with HIV, and the idea of a therapeutic GBV-C biovaccine in persons
with HIV is an important one to consider, especially in resource poor countries
where AIDS death rates remain high.”

GBV-C is a
non-dangerous infection that is transmitted in similar ways to HIV. An earlier
meta-analysis of studies involving 1294 HIV-positive people showed that
co-infection with GBV-C was associated with a 59% reduction in the relative
risk of death. This finding is consistent with laboratory research which
indicate that GBV-C induces cytokines that inhibit HIV, lower T-cell
activation, block IL-2 mediated CD4 T-cell proliferation and reduce
expression of the HIV entry receptors, CCR5 and CXCR4.

Despite these results,
many doctors remain unconvinced of the beneficial effects of infection with
this virus. In particular, the effect of incident GBV-C infection on disease
progression in people already infected with HIV is uncertain.

Investigators from the
Viral Activation Transfusion Study (VATS) believed that their cohort of
people with advanced HIV disease provided an ideal population in which to
examine the impact of prevalent and incident GBV-C infection on all-cause
mortality.

Blood samples obtained
from the study participants before and after blood transfusion, were retrospectively
tested for GBV-C antibodies and RNA. The investigators were therefore able to
accurately determine whether participants were infected with this virus at baseline, or
acquired the infection during follow-up. The study was conducted in 1996-97,
shortly after the introduction of effective antiretroviral therapy.

A total of 489
people, all of whom had AIDS, were included in the authors’ analyses. At
baseline, 60% of people were negative for both GBV-C antibodies and RNA, 33%
had antibodies to the infection and 7% had detectable GBV-C RNA. Participants were
followed for a median of 8.4 months. A total of 267 people (55%) died and a
further 9% withdrew from the study or were lost to follow-up.

Survival was
significantly better for people with detectable GBV-C at baseline compared to those who did not (p = 0.02). The association between GBV-C viraemia and
improved survival remained significant after adjusting for several important
baseline characteristics associated with outcomes in people with HIV,
including CD4 cell count, HIV viral load and use of combination antiretroviral
therapy (adjusted HR = 0.42; 95% CI, 0.24-0.73).

A total of 39 people (13%) acquired GBV-C infection during the course of the study. Even
after adjusting for other prognostic factors, people with GBV-C RNA after
incident infection had a substantial reduction in their mortality risk
(adjusted HR = 0.22; 95% CI, 0.08-0.58) compared to the people who remained
GBV-C RNA-negative.

“We found that GBV-C
viremia is associated with lower mortality in HIV-infected patients, after adjusting
for baseline HIV viral load, CD4 count and HAART status,” write the
investigators. “In addition, we found a significant reduction in mortality
associated with incident GBV-C infection during follow-up…even after
controlling for time-updated HIV disease markers.”

Dr Gretch believes
that the study’s findings are potentially of huge significance.

He stresses that GBV-C
is so safe in humans that blood donations in the US are not screened for its
presence, and also notes that the virus is “a natural bio-antagonist for HIV.”

“Still today,” he
concludes, “the death rate from HIV remains enormous, especially in resource
poor countries, and we have yet to see a trial of GBV bio-vaccination in
HIV-infected populations with high death risk…it’s time for an interventional
GBV biotherapy therapy study in persons with life-threatening HIV infections.”

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.